From 1967 to 1968, Prentiss co-starred with her husband Richard Benjamin in the CBS sitcom He & She, for which she received a nomination for Primetime Emmy Award for Outstanding Lead Actress in a Comedy Series.

Prentiss was born Paula Ragusa in San Antonio, Texas, the elder daughter of Paulene (née Gardner) and Thomas J. Ragusa, a social sciences professor at San Antonio's University of the Incarnate Word.

[7] In 1958, while studying drama at Northwestern University, she met future husband Richard Benjamin, who impressed her with his sophistication and height (he was taller than she was).

[11] The film was a hit and response to Prentiss and Hutton was very favorable, so MGM decided to reteam them in three more comedies, promoting them as a new William Powell and Myrna Loy: The Honeymoon Machine (1961) with Steve McQueen, Bachelor in Paradise (1961) with Bob Hope, and The Horizontal Lieutenant (1962).

Howard Hawks cast her as the female lead opposite Rock Hudson in Man's Favorite Sport?

"[15] Prentiss appeared on stage in a production of As You Like It in 1963 at the New York Shakespeare Festival in Central Park.

"One day during shooting," she told People in 1976, "I just climbed up the ropes to the catwalk and started walking the beams.

In 1969 she appeared Off-Broadway in the double production, Arf and The Great Airplane Snatch, directed by Benjamin.

[17] She was the female lead in Crazy Joe (1974) and had a small but pivotal part in The Parallax View (1974) with Warren Beatty.

Prentiss guest starred on TV shows like Murder, She Wrote and Burke's Law.